Design and synthesis of 2-oxo-1,2-dihydropyridine-3-carboxamide derivatives as new modulators of endocannabinoid system.

Cannabinoid receptors and endocannabinoid ligands, together with the enzymes implicated in endocannabinoid biosynthesis, degradation and transport constitute the endocannabinoid system (ECS). It is involved in several physiological and pathological processes. Previously in a research program focused on the discovery of new CBR ligands, a series of 2-oxo-1,2- dihydropyridine-3-carboxamide derivatives was developed. These compounds showed potent and selective affinity toward CB2R. Moreover, it was discovered that the substituent in position C5 of the pyridine ring was the main responsible for the functional activity of this class of compounds. After the insertion of a methyl group at the C6 position of the pyridine ring was investigated. It was found that the presence of a small substituent in that position did not affect both the CBR affinity and the functional activity within this class of compounds. In this thesis, novel potential CBR ligands were synthesized modifying the 2-oxo-1,2-dihydropyridine-3-carboxamide nucleus with different approaches: 1) shift of the methyl group of 6-methyl-2-oxo-1,2-dihydropyridine-3-carboxamide derivatives from C6 to C4 position of the pyridine ring; 2) shift of the substituents of 2-oxo-1,2-dihydropyridine-3-carboxamide derivatives from C5 to C4 position of the pyridine ring; 3) insertion of a further substituent in position 4 of the pyridine ring in the 2-oxo-1,2-dihydropyridine-3-carboxamide derivatives